Biology Reference
In-Depth Information
described above, such as OPTIC,
39
PhIGs,
40
and RSD.
41
Given the
appropriate data, phylogenetic methods are likely to produce more accurate
models of ancestral sequences and should therefore yield more accu-
rate orthology predictions.
Appreciation of the important concept of the implicit hierarchy of
orthologous relations has prompted the development of several
approaches: the LOFT
42
(Levels of Orthology From Trees) package,
which interactively interprets gene trees in the context of species trees;
the PHOG
43
approach, which resolves orthology at each taxonomy node
using explicit modeling of the ancestral genomes with sequence profiles;
the eggNOG
32
database, which provides orthologous groups defined at
a few major clades of organisms; and OrthoDB,
31
which delineates
orthologous groups at each radiation node of the species phylogeny and
provides navigation along the tree hierarchy through an interactive Web
interface. Indeed, the precise delineation of such evolutionary relation-
ships is integral to comparative genomics, where the perspective, in terms
of the range of species considered, defines the types of questions that can
be asked (Table 2).
Interrogating orthologous group data by phylogenetic gene copy
number profiles facilitates the identification of groups with species- or
lineage-specific losses or expansions as well as the identification of com-
mon single-copy genes. Such single-copy orthologs are most likely to
retain the same ancestral function and therefore evolve under similar evo-
lutionary constraints, making them an ideal data set for evolutionary
studies such as the estimation of rates of molecular evolution along line-
ages and the dating of their radiation times (Fig. 3). Measures of genome
divergence that are not obviously related, such as protein identity of
orthologs, conservation of their genomic synteny, and rates of gene
losses, are in fact well correlated,
44
indicating that global factors affect the
fixation rate of different kinds of mutations in a population. For exam-
ple, insects evolve about two to three times faster than vertebrates, result-
ing in both more divergent orthologs and more gene losses.
Interestingly, even single-copy orthologs can be lost from some species,
implying that they are not absolutely indispensable,
45
yet of course they
are under substantially stronger selection than multi-copy orthologs and
therefore have slower rates of losses. The accurate alignment of one-to-one
